Analysis of recombination hot regions based on inference of intensity of recombination at nucleotide level in pathogenic bacterial species

• Project/Area Number: 15K21554
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Genome biology; Genetics/Chromosome dynamics
• Research Institution: National Institute of Infectious Diseases (2016-2018); Kurume University (2015)
• Principal Investigator: Yahara Koji 国立感染症研究所, 薬剤耐性研究センター, 主任研究官 (70542356)
• Research Collaborator: Falush Daniel Max Planck Institute ; Didelot Xavier Imperial College London ; Maiden Martin University of Oxford ; Sheppard Samuel Swansea University ; Kobayashi Ichizo 東京大学
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 組換え / 進化 / 細菌 / ゲノム / 自然選択 / 病原性 / 集団遺伝 / 情報

Outline of Final Research Achievements

This project elucidated landscape of realized homologous recombination and recombination “hot” region with elevated rates relative to the genome average in 11 human pathogens of major public health importance. It gave answers to the following questions: (A) Do virulence genes show elevated rates of recombination? (B) Do genomic regions carrying recurrent amino acid changes under diversifying selection show elevated rates of recombination? (C) Are there shared recombination “hot” or “cold” genes that show consistently high or low recombination rate among the species? (D) Is horizontal gene transfer between species related to the recombination “hot” region? Furthermore, another methodological improvement and its application to Helicobacter pylori enabled elucidation of novel population structure and amino acid changes that were important during its evolution.

Academic Significance and Societal Importance of the Research Achievements

1 塩基単位の高解像度での組換えのランドスケープとホット領域を、組換え率の最も高い種から低い種まで11種にわたって明らかにしたのは、これが全生物で初めてであった。また、生物学の長年の関心事であるアミノ酸置換率と組換え率の関係について、微生物ゲノムの中から初めて定量的なエビデンスを示すことができた。いずれも、生物学一般にとって意義深い成果だと言える。公衆衛生に重要な病原細菌種を対象とした点で、医学的にも意義深い。

Research Products

• [Int'l Joint Research] University of Bath/University of Oxford/Imperial College London(英国)
• [Int'l Joint Research] Institute of Molecular and Cell Biology(ポーランド)
• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Int'l Joint Research] UMAE Pediatria, IMSS/Instituto Politecnico Nacional, ENCB(メキシコ)
• [Int'l Joint Research] Instituto Nacional de Cancerologia(コロンビア)
• [Int'l Joint Research]
• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Int'l Joint Research] University of Bath/Swansea University/University of Bristol(英国)
• [Int'l Joint Research] ENCB/UMAE(メキシコ)
• [Int'l Joint Research] Universita´ di Pisa(イタリア)
• [Int'l Joint Research] Instituto Nacional de Cancerologia(コロンビア)
• [Int'l Joint Research] Swansea University/Imperial Colledge London/University of Oxford(英国)
• [Int'l Joint Research] Institute of Molecular and Cell Biology(ポーランド)
• [Int'l Joint Research] Karolinska Institutet(スウェーデン)
• [Int'l Joint Research] Wayne State University(米国)
• [Int'l Joint Research] nstituto Politecnico Nacional, ENCB(メキシコ)
• [Int'l Joint Research]
• [Int'l Joint Research] Swansea University/University of Oxford/Imperial College London(United Kingdom)
• [Journal Article] Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas. (2017)
  • Author(s): Thorell K, Yahara K, Berthenet E, Lawson DJ, Mikhail J, Kato I, Mendez A, Rizzato C, Bravo MM, Suzuki R, Yamaoka Y, Torres J, Sheppard SK, Falush D.
  • Journal Title: PLoS Genet Volume: 13(2) Issue: 2 Pages: 1-21
  • DOI: 10.1371/journal.pgen.1006546
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide survey of codons under diversifying selection in a highly recombining bacterial species, Helicobacter pylori. (2016)
  • Author(s): ・Koji Yahara, Yoshikazu Furuta, Shinpei Morimoto, Chie Kikutake, Sho Komukai, Dorota Matelska, Stanisław Dunin-Horkawicz, Janusz M. Bujnicki, Ikuo Uchiyama, Ichizo Kobayashi
  • Journal Title: DNA Research Volume: - Issue: 2 Pages: 135-43
  • DOI: 10.1093/dnares/dsw003
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Landscape of Realized Homologous Recombination in Pathogenic Bacteria. (2015)
  • Author(s): Koji Yahara, Xavier Didelot, Keith A. Jolley, Ichizo Kobayashi, Martin C.J. Maiden, Samuel K. Sheppard and Daniel Falush
  • Journal Title: Molecular Biology and Evolution Volume: 33 Issue: 2 Pages: 456-471
  • DOI: 10.1093/molbev/msv237
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Population genomic studies of microbial recombination, phylogeny, and population structure (2019)
  • Author(s): 矢原耕史
  • Organizer: 日本ゲノム微生物学会
  • Invited
• [Presentation] Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas (2018)
  • Author(s): 矢原 耕史*, Kaisa Thorell*, Elvire Berthenet, Daniel J. Lawson, Jane Mikhail, Ikuko Kato, Alfonso Mendez, Cosmeri Rizzato, Maria Mercedes Bravo, 鈴木 留美子,山岡 吉生, Javier Torres, Samuel K. Sheppard, Daniel Falush
  • Organizer: 日本進化学会
• [Presentation] Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas - showcase of stratified chromosome painting - (2017)
  • Author(s): Koji Yahara*, Kaisa Thorell*, Elvire Berthenet, Daniel J. Lawson, Jane Mikhail, Ikuko Kato, Alfonso Mendez, Cosmeri Rizzato, Mar?´a Mercedes Bravo, Rumiko Suzuki, Yoshio Yamaoka, Javier Torres, Samuel K. Sheppard, Daniel Falush
  • Organizer: Applied Bioinformatics and Public Health Microbiology 2017
  • Int'l Joint Research
• [Presentation] Elucidation of recombination hot regions under selection in bacteria (2017)
  • Author(s): Koji Yahara
  • Organizer: Recent Advances in Biological Sciences: A Roadmap for Island Communities
  • Int'l Joint Research / Invited
• [Presentation] Elucidation of recombination hot regions and population structure in bacteria (2016)
  • Author(s): Koji Yahara
  • Organizer: International Symposium on Genome Microbiology
  • Place of Presentation: Tokyo Institute of Technology
  • Year and Date: 2016-03-06
  • Int'l Joint Research
• [Presentation] Methods for studying recombination hot regions and population structure in bacteria (2016)
  • Author(s): Koji Yahara
  • Organizer: SMBE Satellite Workshop on Genome Evolution in Pathogen Transmission and Disease
  • Place of Presentation: Shiga Lake Hotel
  • Year and Date: 2016-02-23
  • Int'l Joint Research / Invited
• [Presentation] The landscape of realized homologous recombination in pathogenic bacteria (2016)
  • Author(s): 矢原耕史、Xavier Didelot、Keith A Jolley、小林一三、Martin C. J. Maiden、Samuel K. Sheppard and Daniel Falush
  • Organizer: 日本進化学会
  • Place of Presentation: 東京工業大学
• [Presentation] 種内多数のゲノムデータから組換えの痕跡と集団構造を推定する手法とその応用 (2016)
  • Author(s): 矢原耕史
  • Organizer: 第77回インシリコ・メガバンク研究会
  • Place of Presentation: 東北メディカルメガバンク
  • Invited
• [Presentation] 病原細菌の遺伝情報の水平伝達 -集団ゲノミクスのアプローチ- (2016)
  • Author(s): 矢原耕史
  • Organizer: 日本分子生物学会
  • Place of Presentation: パシフィコ横浜
  • Invited
• [Presentation] A novel method for efficient inference of recombination hot regions in bacterial genomes and its application to 200 C. jejuni genomes (2015)
  • Author(s): Koji Yahara, Xavier Didelot, M. Azim Ansari, Samuel K. Sheppard and Daniel Falush
  • Organizer: The 18th International workshop on Campylobacter, Helicobacter and related organisms
  • Place of Presentation: Energy Events Centre in Rotorua
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Efficient inference of recombination hot regions in bacterial genomes (2015)
  • Author(s): Koji Yahara, Xavier Didelot, M. Azim Ansari, Samuel K. Sheppard and Daniel Falush
  • Organizer: Conference to celebrate the opening of our new MRC CLIMB centre “What can we learn from hundreds of bacterial genomes?”
  • Place of Presentation: Swansea University
  • Year and Date: 2015-10-22
  • Int'l Joint Research
• [Presentation] 病原細菌の種内多数のゲノムデータから組換えのホット領域と集団構造を推定する新たなアプローチ (2015)
  • Author(s): 矢原耕史
  • Organizer: 生命科学データ解析の方法論と健康科学への応用
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2015-10-17
  • Int'l Joint Research / Invited